- Degradation kinetics of gonadorelin in aqueous solution
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The degradation kinetics of gonadorelin were investigated systematically with reversed-phase high-performance liquid chromatography. The stability- indicating properties of this system were checked with photodiode array detection and by comparison with capillary zone electrophoretic analysis. Influences of gonadorelin concentration, pH, temperature, buffer ions, and ionic strength on the degradation kinetics were studied. The pH-Iog κ(abs) profile can be divided into three pads, a proton, a solvent, and a hydroxyl- catalyzed section, with different degradation products. These degradation products were characterized by mass using LC-MS. Gonadorelin is most stable at pH 5-5.5 with a half-life of 70 days at 70 °C. The overall degradation rate constant as a function of the temperature under acidic and alkaline conditions obeys the Arrhenius equation. The gonadorelin concentration and the concentrations of acetate, phosphate, borate, and carbonate buffer have no influence on the decomposition rate of the κ(abs). Increasing ionic strength led to higher κ(abs) at pH 2 and lower κ(abs) at pH 9, but influences were relatively small.
- Hoitink, Marnix A.,Beijnen, Jos H.,Bult, Auke,Van Der Houwen, Oeds A. G. J.,Nijholt, Jack,Underberg, Willy J. M.
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- Characterization of the solution degradation products of histrelin, a gonadotropin releasing hormone (LH/RH) agonist
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The degradation products of histrelin (1, Glu-His-Trp-Ser-Tyr-(D-N(im)-bzl-His)-Leu-Arg-Pro-NHEt) were determined in aqueous solution at pH 5.4 and 87°C over an 18-day period (47% degradation). These degradation products (2-5) resulted from the cleavage of Glu-His and Trp-Ser peptide bonds, His-Trp diketopiperazine formation, and racemization of serine and histidine residues.
- Oyler,Naldi,Lloyd,Graden,Shaw,Cotter
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p. 271 - 275
(2007/10/02)
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- Characterization of the degradation products of luteinizing hormone releasing hormone
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The degradation products of luteinizing hormone releasing hormone [LH/RH; 1; gonadorelin releasing hormone (GnRH); 2] were determined in aqueous solution (pH 6.5) at 25, 37, 50, and 80 °C. The predominant route of degradation involved the cleavage of the 2 to the free acid form in peptides 4 and 10. Racemization of the serine and histidine residues to give peptides 2 and 3 was a second route of degradation.
- Motto,Hamburg,Graden,Shaw,Cotter
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p. 419 - 423
(2007/10/02)
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